There is substantial evidence that the hormones gastrin, secretin, and cholecystokinin (CCK) exert trophic influences on normal stomach and liver. To date, however, little work has been done to investigate possible trophic influences of these hormones on carcinomas arising in these organs. The nude mouse is a unique experimental animal which is well-suited to study this question because it will readily accept subcutaneous xenografts of human and animal cancers. Human and animal carcinomas arising in stomach and liver and established by implantation in nude mice will be used to investigate possible trophic effects of the hormones gastrin, secretin, and CCK. After these tumors have been transplanted subcutaneously into nude mice, injections of gastrin, secretin, and CCK will be administered for specified periods of time, and the growth of the tumors will be recorded. The animals will then be sacrificed and the effects of the hormones on tumor size, pattern of metastases, and histology will be determined. Morphometric study of the tumor implants will be carried out; and determinations of DNA, RNA, and protein content of the implanted tumors will be done. Serological markers (carcinoembryonic antigen or alpha-fetoprotein) also will be measured. We have now constructed dose-response curves for mice receiving pentagastrin and CCK over a 5-log range of doses, thus establishing a pharmacologically active dose with respect to trophic actions in the nontumor-bearing mouse. We have utilized exogenous pentagastrin using human gastric adenocarcinoma line SLU-048 in the nude mouse and found no trophic effect. Further studies using CCK and human cholangiocarcinoma line SLU-132 have indicated a growth-retarding effect of this hormone as well as an increase in CEA production. Such studies will: (1)\establish whether gastrin, secretin, and CCK exert growth-modulating effects on these human and animal carcinomas in the nude mouse model; (2)\elucidate mechanisms involved in any trophic effect observed; and (3)\suggest potential roles for novel approaches to these diseases in man (including surgical procedures). (C)